Identifying candidate genes for blood pressure quantitative trait loci using differential gene expression and a panel of congenic strains

Hypertens Res. 1998 Dec;21(4):289-96. doi: 10.1291/hypres.21.289.

Abstract

The most difficult step in dissecting the molecular basis of a quantitative trait is proceeding from chromosomal locations associated with this trait (i.e., quantitative trait locus, QTL) to determining what gene(s) in the QTL region is causative. Using standard positional cloning methodology to identify candidate genes for a particular QTL has three drawbacks: 1) it is labor intensive; 2) defining variants in genes causing quantitative variation from sequence information alone is difficult or impossible; and 3) many (or most) genes in a particular chromosomal interval will not be relevant for a specific disease/trait because they are not expressed in critical candidate organs. Instead of positional cloning, we propose using a panel of congenic strains, where each carries an allele for a different QTL on a similar genetic background, in conjunction with identification of differentially-expressed genes in target organs of inbred strains of contrasting phenotype. This will identify genes having altered expression in organs critical to regulating blood pressure and the development of hypertension. Radiation hybrid mapping of such genes will result in a transcription map of differentially-expressed genes in a target organ of a rat model of genetic hypertension. This approach could rapidly identify genes mapping to genomic regions near QTL, which will be strong candidates to explain, in part, the observed strain differences in blood pressure. This novel approach, which uses a panel of congenic strains to facilitate the mapping and subsequent identification of differentially-expressed and QTL-associated genes, should be applicable to any genetic model for identifying candidate genes located near QTL, given the availability of a panel of congenic strains.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.
  • Review

MeSH terms

  • Animals
  • Animals, Congenic / genetics*
  • Animals, Congenic / physiology
  • Blood Pressure / physiology*
  • Chromosome Mapping*
  • Gene Expression / physiology*
  • Genetic Techniques*
  • Humans
  • Quantitative Trait, Heritable*